Highly stereoselective alpha-hydroxyalkylation/chlorination of alpha,beta-acetylenic ketones - An efficient approach to beta-halogeno Baylis-Hillman adducts

A highly stereoselective method for the synthesis of (E)-beta-halogeno Bayl is-Hillman adducts has been developed. The new method involves a tandem alp ha-hydroxyalkylation/beta-chlorination of alpha,beta-acetylenic ketones by using TiCl4 as the chlorine source for alpha,beta-conjugate addition, and c oncurrently as the Lewis acid promoter for the carbonyl addition. The new s ystem tolerates a broad scope of reactants in which aliphatic and aromatic alpha-acetylenic ketones can be subjected to the conjugate addition. Both a liphatic and aromatic aldehydes can also be employed as electrophilic accep tors. Good yields (61-88%) and high E/Z stereoselectivity have been obtaine d for the nine examples which were examined, only in one case was E/Z selec tivity of 17/1 observed and the two individual isomers are separable via ha sh column chromatography. (C) 2000 Elsevier Science Ltd. All rights reserve d.